{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPreoperative chemoradiation therapy (CRT) is increasingly used to treat cancer, but individual responses to this treatment are highly variable, with poorly responsive patients facing significant clinical risks. Although the study in PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "does not directly address RFLNA, the growing need for predictive markers in such therapeutic settings underscores the broader importance of delineating the molecular pathways that control cellular structure and function.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent research has identified RFLNA as encoding refilin A, a protein that binds filamin and interacts with myosins to regulate the organization of the actin cytoskeleton. Specifically, refilin A plays a pivotal role in assembling perinuclear actin caps—structural actin bundles that influence nuclear shape during cell migration and differentiation. Disruptions in this mechanism have been directly linked to skeletal pathologies, as demonstrated by a homozygous frameshift mutation in RFLNA found in a patient with spondylocarpotarsal synostosis syndrome (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings implicate RFLNA as essential for proper cytoskeletal remodeling and nuclear morphology regulation. In the context of developmental skeletal disorders, defective RFLNA function—in particular, its inability to support robust actin bundle formation and perinuclear actin cap assembly—may be a critical pathogenic mechanism, suggesting that further investigation into its roles could also identify new biomarkers or therapeutic targets in other settings, including personalized cancer therapies.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jin C Kim, Ye J Ha, Seon A Roh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel single-nucleotide polymorphism markers predictive of pathologic response to preoperative chemoradiation therapy in rectal cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Radiat Oncol Biol Phys (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijrobp.2012.12.018"}], "href": "https://doi.org/10.1016/j.ijrobp.2012.12.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23490283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23490283"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hitomi Shimizu, Satoshi Watanabe, Akira Kinoshita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a homozygous frameshift variant in RFLNA in a patient with a typical phenotype of spondylocarpotarsal synostosis syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-019-0581-9"}], "href": "https://doi.org/10.1038/s10038-019-0581-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30796325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30796325"}]}]}]}